DIGOXIN DYSRHYTHMIAS  NO MORTALITY BENEFIT ( DIGITALIS INVESTIGATION GROUP),1997

DIGOXIN  Inhibition of Na+k+-ATPase pump  Parasympathetic activation  Sympathetic inhibition  Inhibition of renin release from the kidney

MORTALITY- undiagnosed digitalis toxicity  Study DREFIUS AND COLLEAGUES  Atrial tachycardia with block – 100% mortality when digoxin is continued 16% when digoxin is discontinued  Junctional tachycardia- 81% mortality when digoxin continued 16% when digoxin dicontinued

Therapeutic levels  Previous levels : 1 to 2 ng/ml  Current level : 0.5 to 1.5 ng/ml  0.125mg has the similar haemodynamic and autonomic effects like 0.25  Turnaround level : 1ng/ml (modest 6% mortality reduction in levels 0.5 to 0.8 ng/ml, no benefit 0.9 to 1.1 ng/ml, more than 1.2 ng/ml mortality increased by 12%)

EFFECTS OF DIGOXIN ON ECG- THERAPEUTIC  Prolongation of P-R interval  Slowing of ventricular response in atrial flutter and atrial fibrillation  Isolated A-V junctional escape impulses  Conversion of atrial arrythymias to sinus rhythm

EXCESSIVE OR TOXIC EFFECTS  ATRIAL TACHYCARDIA WITH BLOCK  Non paroxysomal junctional tachycardia  A-V dissociation  Second or third degree A-V Block  SA block  AV junctional rhythm

UNEQUIVOCAL SIGNS  Isolated VPC  Ventricular bigeminy  Multifocal VPC  Ventricular tachycardia  Bidirectional VT  Ventricular fibrillation

THERAPEUTIC EXCESSIVE TOXIC 1)ST-T CONFIGURATION 2)P-R PROLONGATION (200 TO 300 MS) 3) AF- VENTRICULAR SLOWING NODAL ESCAPE( AVERAGE VENTRICULAR RATE 50 TO 70) 1)SINUU RHYTHM AF or AT with irregular ventricular response 2)NODAL TACHYCARDIA WITH AV DISSOCIATION 3)S-A BLOCK- ---NODAL RHYTHM WITH RETROGRADE CONDUCTION 4) SECOND DEGREE OR COMPLETE AV BLOCK 1)BIGEMINY 2) MULTI FOCAL VPC OR VPC IN RUNS 3)BIDIRECTIONAL VT 4)VENTRICULAR FIBRILLATION CONTINUE REDUCE STOP

Digoxin –sinus node  No change in Automaticity  High doses depression in the automaticity of sinus node(it can also increase with toxic doses)  Therapeutic doses can impair sinoatrial conduction  Sick sinus syndrome –lengthening of sinus node recovery time and sino atrial conduction time  If digoxin therapy is indicated in heart failure sss –EPS  Corrected SNRT MORE THAN 1000 IS predictive of further lengthening of pauses

Digoxin -Atrium  Atrium more sensitive than the sinus node for direct effect on digoxin  Decreased effective refractory period  Increased conduction velocity Toxic doses – conduction velocity can be decreased Decreased membrane responsiveness

Digoxin –AV node  Effective refractory period of digoxin is prolonged (combination of vagal and direct effect)  Conduction velocity is decreased  Decreased amplitude and upstroke velocity of action potential  Therapeutic slowing of ventricular respone is due to decremental conduction within the node  Second or third degree AV block –digitalis intoxication is due to failure of propogation within the node

DIGOXIN –His Purkenje system  Increased automaticity –enchanced phase 4 depolarization  Increased excitability  Decreased conduction velocity  Increased effective refractory period TOXIC DOSES – decreased membrane responsiveness decreased effective refractory period

DIGOXIN - VENTRICLES  Decreased membrane responsiveness  Increased conduction velocity  Decreased effective refractory period

Low concentration  Resting membrane potential unchanged  Action potential amplitude unchanged  Time of course of depolarization and repolarization remains unchanged

High concentrations  Progressive loss of resting potential  Decreased upstroke of action potential  Shortening of plateau phase  Increased rate of spontaneous diastolic depolarization

SA BLOCK  Even in therapeutic doses  Recognised by sinus rhythm group beating shortened PP interval pause less than twice the shortest PP cycle

ATRIAL TACHYCARDIA WITH BLOCK  Block secondary to lengthening AV node refractory period and rapid atrial rate  When digoxin is discontinued conduction improves before converting to sinus rhythm – brief period of 1:1 conduction  Ventriculo phasic behavior of P’ P’ interval  P’P’ interval containing R wave is shorter than P’P’ interval without the R wave

JUNCTIONAL TACHYCARDIA  Underlying rhythm can be sinus, atrial fibrillation, atrial flutter, atrial tachycardia  Retrograde conduction is usually absent due to AV block created by digitalis  V1 – QRS morphology helps to differentiate between junctional tachycardia from fascicular VT

FASCICULAR VENTRICULAR TACHYCARDIA QRS width narrower than usual Rsr’ pattern in V1 ANTEROSUPERIOR FASICLE-right axis deviation POSTERO INFERIOR FASCICLE-left axis deviation

Bidirectional ventricular tachycardia  Beat to beat alteration of normal QRS AXIS IN LIMB LEADS  QRS width narrower than usual  Ventricular rate 140 to 180/m  QRS ALTERNANS in V1  Mortality 100%  Triggered activity due to DAD is the predominant cause

Ventricular bigeminy  Mc manifestations of digoxin overdosage – ventricular extrasystoles  They are not diagnostic of digoxin toxicity

Concealed ventricular bigeminy

Digitalis effect  Prolonged PR interval  ST segment depression  Decreased amplitude of T waves  Shortened QT  Increased U wave amplitude

Digitalis effect and toxicity  Digoxin effect  Inverse check mark sign of ST manifest in leads which have dominant upright QRS ONLY  Downward slope of ST begins from isoelectric base  T wave raises above the baseline before becoming isoelectric  Digoxin toxicity  Inverse check mark sign of ST manifest in leads which have dominant upright QRS ONLY as well as leads with dominant negative QRS  If the beginning of the ST is already depressed it denotes toxicity or primary ST depression such as ischaemia  T wave does not raises above the baseline

Increased sr digoxin levels  Lean body mass  Decreased renal excretion hypokalemia,beta blockers,congestive heart failure,renal disease,elderly patients  Decreased non renal clearance quinidine,verapamil,amiodarone,propafenone  Decreased conversion in the gut erythromycin,tetracycline